Cytoplasmic aconitate hydratase (ACO1)
The protein contains 889 amino acids for an estimated molecular weight of 98399 Da.
Iron sensor. Binds a 4Fe-4S cluster and functions as aconitase when cellular iron levels are high. Functions as mRNA binding protein that regulates uptake, sequestration and utilization of iron when cellular iron levels are low. Binds to iron-responsive elements (IRES) in target mRNA species when iron levels are low. Binding of a 4Fe-4S cluster precludes RNA binding.', 'Catalyzes the isomerization of citrate to isocitrate via cis-aconitate. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs150373174 | |
| dbSNP:rs3814519 | |
| dbSNP:rs34630459 |
Biological Process
Cellular iron ion homeostasis
Citrate metabolic process
Intestinal absorption
Post-embryonic development
Regulation of translation
Response to iron(II) ion
Tricarboxylic acid cycle
Cellular Component
Cytoplasm
Cytosol
Endoplasmic reticulum
Extracellular exosome
Golgi apparatus
Mitochondrion
Obsolete cell
The reference OMIM entry for this protein is 100880
Aconitase 1, soluble; aco1
Aconitate hydratase, soluble
Aconitase, soluble; acons
Iron-responsive element-binding protein 1; ireb1
Ire-binding protein 1; irebp1; irebp
Iron regulatory protein 1; irp1
DESCRIPTION
Soluble aconitase is a bifunctional protein with mutually exclusive functions as an iron responsive element (IRE)-binding protein involved in the control of iron metabolism or as the cytoplasmic isoform of aconitase. Aconitases are iron-sulfur proteins that require a 4Fe-4S cluster for their enzymatic activity, in which they catalyze conversion of citrate to isocitrate (EC 4.2.1.3) (Eisenstein, 2000).CLONING
Rouault et al. (1990) used RNA affinity chromatography and 2-dimensional gel electrophoresis to isolate IREBP for protein sequencing. They used an oligonucleotide probe derived from the peptide sequence to isolate a cDNA encoding a protein of 87 kD. The corresponding mRNA of about 3.6 kb was found in a variety of cell types.GENE FUNCTION
Aconitase-1 functions as a cytoplasmic IRE-binding protein (IREBP). IREs are translational regulatory sequences in the 5-prime UTR of ferritin (see 134790) mRNA and in the 3-prime UTR of transferrin receptor mRNA (190010). The cytoplasmic IREBP interacts with the IREs of these mRNAs. The iron status of the cell determines the ability of IREBP to bind to an IRE through reversible oxidation-reduction of sulfhydryl groups that are critical for the high-affinity RNA-protein interaction. Thus, IREBP plays a central role in cellular iron homeostasis by regulating ferritin mRNA translation and TFRC mRNA stability (Hentze et al., 1989). Eisenstein (2000) reviewed of the role of the iron regulatory proteins, IRP1 and IRP2 (147582), and the molecular control of mammalian iron metabolism. Meyron-Holtz et al. (2004) found that IRP2-null cells misregulated iron metabolism when cultured in 3 to 6% oxygen, which is comparable to physiologic tissue concentrations, but not in 21% oxygen, a concentration that activated IRP1 and allowed it to substitute for IRP2. Thus, IRP2 dominates regulation of mammalian iron homeostasis because it alone registers iron concentrations and modulates its RNA-binding activity at physiologic oxygen tensions. Condo et al. (2010) demonstrated that the extramitochondrial form of frataxin (FXN; 606829) directly interacted with IRP1 through the 'iron-sulfur switch' mechanism. Cytosolic aconitase defect and consequent IRP1 activation occurring in Friedreich ataxia cells were reversed by the action of extramitochondrial frataxin.BIOCHEMICAL FEATURES
- Crystal Structure IRP1 binds IREs in mRNAs, to repress translation or degradation, or binds an iron-sulfur cluster, to become a cytosolic aconitase enzyme. Walden et al. (2006) determined the crystal structure of IRP1 bound to ferritin H (134770) IRE to 2.8-angstrom resolution. The IRP1:ferritin H IRE complex showed an open protein conformation compared with that of cytosolic aconitase. The extended, L-shaped IRP1 molecule embraced the IRE stem loop through interactions at 2 sites separated by about 30 angstroms, each involving about a dozen protein:RNA bonds. Walden et al. (2006) concluded that extensive conformational changes related to binding the IRE or an iron-sulfur cluster explain the alternate functions of IRP1 as an mRNA regulator or enzyme.MAPPING
In studies of man-Chinese hamster somatic cell hybrids, Westerveld et al. (1975) showed that human gal-1-p uridyl transferase (GALT; 606999) and aconitase are syntenic. Povey et al. (1976) assigned the ACO1 gene to chromosome 9. ACO1 and GALT are on chromosome 9p in man and on chromosome 4 in the mouse (Nadeau and Eicher, 1 ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 100880 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed